This project is a clinical investigation of transplant recipients. It embraces two major objectives: The first objective is to test the efficacy of new monoclonal antibodies (mAb) for control of rejection that will be applicable to recipients of all types of organ allografts. The second is to characterize the mechanisms of action of the mAb and the consequences on the immune system, particularly the effects on donor-specific nonresponsiveness.. New mAbs are being developed and selected for clinical trial. Initially, we will begin a randomized trial of the anti-ICAM (intercellular adhesion molecule) mAb (anti CD54) which has already undergone pilot clinical studies. Shortly thereafter clinical trials using anti CD4 mAbs, which are currently being evaluated in Cynomolgus recipients, will be instituted. We intend to pursue new opportunities for improvement of rejection control by targeting with increasing selectivity only immunologically activated cells. Ultimately, we are seeking to induce donor-specific unresponsiveness, preferably without the need for the long-term treatment that is required with conventional immunosuppression. Evaluation of immune responses in patients will involve several simultaneous approaches. Circulating or graft infiltrating cells are enumerated by flow cytometry using a panel of mAbs and newer techniques that permit detection of cells bearing high specific surface antigens such as those associated with memory or suppression. These methods will be combined with tests of the immune function of selected cell populations sorted either from the blood or from cellular infiltrates recovered from graft biopsies. These studies should provide valuable information for the management and improvement of mAb immunosuppression.